Developing RNA Vaccines to Treat Peanut Hypersensitivity

开发治疗花生过敏的 RNA 疫苗

• 批准号: 10570339
• 负责人: Herman F Staats
• 金额: $ 26.08万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-03 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10570339
• 关键词: 2019-nCoV; Address; Adjuvant; Affect; Allergen Immunotherapy; Allergens; Allergic; Allergic Disease; Allergic Reaction; Allergy to peanuts; Anaphylaxis; Antibodies; Antigens; CD8-Positive T-Lymphocytes; COVID-19 pandemic; Cell Degranulation; Clinical; Communicable Diseases; Data; Developed Countries; Development; Dose; Epitopes; Event; Exposure to; FDA approved; Food Hypersensitivity; Formulation; Foundations; Future; Generations; Goals; Human; Hypersensitivity; IgE; IgG(T); Immunization; Immunize; Immunoglobulin A; Immunoglobulin G; Immunotherapeutic agent; Immunotherapy; In Vitro; Individual; Inflammation Mediators; Length; Life; Mediating; Medical; Messenger RNA; Methods; Monitor; Mus; Mutate; Mutation; Nose; Oral; Oral Administration; Package Insert; Persons; Population; Prevalence; Product Approvals; Production; Protein Truncation; Proteins; RNA; RNA vaccine; Research; Risk Reduction; Route; Safety; Serum; Severities; Surface; Symptoms; T cell response; T-Lymphocyte; T-Lymphocyte Epitopes; Technology; Testing; Time; Transfection; Vaccine Production; Vaccines; Western Blotting; allergic response; cell mediated immune response; coronavirus disease; crosslink; desensitization; granulocyte; immunogenicity; improved; in vivo; mast cell; mutant; natural hypothermia; oral immunotherapy; prevent; protein expression; response; vaccine platform

Project Summary/Abstract: Oral immunotherapy with PALFORZIA® is a recently FDA-approved therapy to treat peanut allergy. This therapy requires daily doses of characterized peanut proteins administered orally to peanut hypersensitive individuals. A major limitation of the PALFORZIA® therapy is the potential for the onset of allergic responses and possibly anaphylaxis due to activation of peanut-specific IgE coated mast cells. Development of hypoallergenic peanut proteins devoid of IgE-mediated granulocyte activation potential may address the known safety limitations of therapy with PALFORZIA®. The rise of the SARS-CoV-2 pandemic and rapid production and dissemination of mRNA COVID vaccines has highlighted the benefits of mRNA vaccines to protect against infectious diseases. The goal of this project is to utilize mRNA vaccine technology to express peanut proteins that lack and/or disrupt known IgE epitopes to provide a peanut allergen vaccine that does not induce allergic reactions in hosts hypersensitive to the native allergen. This proposal will utilize the dominant peanut allergen, Ara h 2, which is recognized by majority of peanut allergic individuals and is sufficient to induce hypersensitivity in mice, to develop mRNA vaccines that produce native Ara h 2 or mutant Ara h 2 with mutations in known linear IgE epitopes. The studies described in this proposal will evaluate in vitro protein production, in vitro IgE-mediated granulocyte activation, in vivo immunogenicity, and in vivo allergic disease activation in hosts sensitized to the native allergen. The results from this proposal will generate proof-of-concept preliminary data to support future studies to develop mRNA vaccines expressing multiple peanut proteins to treat peanut- hypersensitivity in allergic hosts.

项目摘要/摘要：使用Palforzia®的口服免疫疗法是最近经FDA批准的治疗 治疗花生过敏。这种疗法需要每天口服给药的特征性花生蛋白 花生超敏人。 Palforzia®疗法的主要局限性是发作的潜力 由于花生特异性IgE涂层肥大细胞的激活而导致的过敏反应和可能的过敏反应。 发育的低过敏性花生蛋白不含IgE介导的粒细胞激活潜力可能 通过Palforzia®解决已知的治疗安全局限性。 SARS-COV-2大流行和 mRNA疫苗的快速生产和传播强调了mRNA疫苗的好处 防止传染病。该项目的目的是利用mRNA疫苗技术表达 缺乏和/或破坏已知IgE表位的花生蛋白，以提供不可能的花生过敏原疫苗 诱导宿主对天然过敏原的过敏反应。该提议将利用主导地位 花生过敏原Ara H 2，大多数花生过敏个体都认可，足以诱导 小鼠的高敏性，开发产生天然Ara H 2或突变H 2突变的mRNA疫苗 在已知的线性IgE表位中。该提案中描述的研究将评估体外蛋白质的产生， 体外IgE介导的粒细胞激活，体内免疫原性和体内过敏性疾病激活 对本地过敏原敏感。该提案的结果将产生概念验证的初步数据 支持未来的研究，以开发表达多种花生蛋白的mRNA疫苗以治疗花生 过敏宿主的超敏反应。